Production of Unilamellar Vesicles Using an Inverted Emulsion

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Weitz D.A. et al. Langmuir 2003, 19, 2870-2879



The article presents a novel emulsification method to prepare unilamellar liposomes ranging between .1 <math>\mu</math>m to 1 <math>\mu</math>m. Previous liposomal preparation techniques such as sonication, electroformation, rehydration of lipid films, extrusion, etc, do not allow simultaneous control of size, encapsulation yield, and lipid composition. In contrast, the technique presented on this paper helps overcome some of these issues by forming vesicles independently one layer at a time as seen in Figure 1 below. First, water is emulsified in oil containing the desired lipid as surfactant. Water drops stabilized at the surface by the lipids will compose the core and inner lipid layer of the vesicles. Second, water is then put in a separate vial, and oil containing lipids is poured on top. These lipids will constitute the outer layer of the vesicles. The emulsified water is then added on top of the second vial containing the two layers of water and oil. The emulsion droplets sink to the bottom passing through the lipid interface and in doing so, the outer layer of the vesicles form as seen in the figure below.

Soft Matter Connection

One of the most important advantages of this technique is the high encapsulation efficiency (98% encapsulation efficiency reported in this publication) that is possible due to the separate layer formation. This is extremely useful for drug delivery applications where high drug loading in vesicles is critical. The separate layer formation is possible through the formation of a stable inversion emulsion. Based on what was covered in class, inverted emulsions are formed when the concentration of emulsified drops increases so much that droplets get so close to each other that it is energetically more favorable for the hydrophilic heads (in the case of an oil-in-water emulsion) to pinch off and form inverted emulsions. Lipid vesicles have been studied since the 1970s and are a fundamental part of Soft Matter. Applications include drug delivery, especially for cancer where liposomes can be targeted to cancerous cells via antibodies. Additionally, lipid vesicles can serve as a platform to gain a better understanding of the cell membrane and its role in cell signaling and transduction.

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Figure 1. Schematic diagram of vesicle preparation via an inverted emulsion.